Achondroplasia

Question 1

What is achondroplasia?

Answer 1

Achondroplasia is the most common cause of disproportionate short stature (dwarfism). It is a type of skeletal dysplasia.

Question 2

Cause of achondroplasia?

Answer 2

Genetics

The achondroplasia gene, fibroblast growth factor receptor 3 (FGFR3), is on chromosome 4. Achondroplasia results from either a sporadic mutation or inheritance of an abnormal copy of this gene. The condition is inherited in an autosomal dominant pattern. Homozygous gene mutations, meaning two abnormal gene copies with one from each parent, is fatal in the neonatal period. Therefore, patients with achondroplasia have one normal gene and one abnormal gene.

Mutations in the FGFR3 gene causes abnormal function of the epiphyseal plates (growth plates). This restricts the bone growth in length, leading to short bones and short stature.

Question 3

Features of achondroplasia?

Answer 3

Patients with achondroplasia have disproportionate short stature. The average height is around 4 feet. The limbs are most affected by reduced bone length. The femur and humerus (proximal limbs) are affected more than the bones of the forearm and lower leg. The spine length is less affected and patients have a normal trunk length. Intelligence and life expectancy are not affected by the condition.

Other features of the condition:

Short digits
Bow legs (genu varum)
Disproportionate skull
Foramen magnum stenosis

Different areas of the skull grow by different methods, some of which are affected more than others. This leads to a disproportionate skull. The skull base grows and fuses via endochondral ossification, which is affected by achondroplasia and leads to a flattened mid-face and nasal bridge and foramen magnum stenosis. The cranial vault grows and fuses via membranous ossification, which is unaffected by achondroplasia and leads to a normal sized vault and frontal bossing (prominent forehead).

Question 4

Associations achondroplasia?

Answer 4

Recurrent otitis media, due to cranial abnormalities
Kyphoscoliosis
Spinal stenosis
Obstructive sleep apnoea
Obesity
Foramen magnum stenosis can lead to cervical cord compression and hydrocephalus

Question 5

Management achondroplasia?

Answer 5

There is no cure for the underlying genetic condition. Management will involve the multidisciplinary team to support the patient with development and maximise functioning:

Paediatricians
Specialist nurses
Physiotherapists
Occupational therapists
Dieticians
Orthopaedic surgeons
ENT surgeons
Geneticists

Leg lengthening surgery can add height, but requires extensive surgery and recovery. It involves cutting the bone (osteotomy) and separating the two parts, creating a gap between them (distraction). Over a long period of time bone will form between the two parts, creating a longer bone. This is controversial and has the potential to lead to significant problems, including chronic pain and reduced function.

Question 6

Prognosis of achondroplasia?

Answer 6

Patients have a normal life expectancy if they are not affected by complications. Patients have a tendency to become relatively overweight due to small stature. There are psychosocial implications to the disproportionate short stature.